It has long been known that phage lysis requires permeabilization of the cytoplasmic membrane by the holin, leading to degradation of the cell wall by the endolysin.  Surprisingly, even after the degradation of the cell wall, lysis of Gram-negative hosts requires the function of a new class of proteins, the spanins, to disrupt the outer membrane (OM), else the progeny virions are left trapped in spherical cells bounded by the intact OM. The prototype two-component spanins are encoded by the Rz and Rz1 genes of phage lambda. Uniquely, Rz1 is completely embedded in the +1 reading frame of Rz. Rz is an inner membrane protein (i-spanin) with an N-terminal transmembrane domain (TMD), whereas Rz1 is an OM lipoprotein (o-spanin). The term spanin is derived from that fact that Rz and Rz1 form a complex via C-terminal interactions, thus spanning the entire periplasm.  Both the i-spanin and o-spanin accumulate as homodimers covalently linked by intermolecular disulfide bonds. A model has been presented in which the Rz₂-Rz1₂ hetero-tetrameric complexes are entrapped by the meshwork of the peptidoglycan until liberated by the muralytic action of the phage endolysin. This allows lateral oligomerization and conformational changes that result in fusion of the IM and OM.  Experiments with spheroplasts labeled with different fluorescent proteins showed that the periplasmic domains of Rz and Rz1 can mediate efficient spheroplast fusion, thus strongly supporting the membrane fusion model. Similar results were obtained with gp11 of phage T1. Gp11 is the prototype unimolecular spanin (u-spanin), a completely different class of spanin in which the same protein molecule has both an N-terminal OM lipoprotein signal and a C-terminal transmembrane domain embedded in the cytoplasmic membrane.  The two-component spanin complex and the u-spanin represent convergent but topologically different solutions to the problem of destruction of the host OM.  Also, given the power of phage genetics and the simplicity of these systems, phage spanins may represent a facile platform for studying the fundamental process of membrane fusion. Finally, spanins may provide a method for creating novel hybrid species of bacteria by virtue of the ability to fuse cytoplasms efficiently.